Apixaban (Eliquis) Dosing Guidelines
For stroke prevention in non-valvular atrial fibrillation, the standard dose is 5 mg orally twice daily, reduced to 2.5 mg twice daily only when patients meet at least 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2
Stroke Prevention in Non-Valvular Atrial Fibrillation
Standard Dosing Algorithm ("2-of-3 Rule")
5 mg orally twice daily is the default dose for most patients with 0 or 1 dose-reduction criteria 1, 2
2.5 mg orally twice daily only when the patient meets at least 2 of the following 3 criteria: 1, 2
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
This "2-of-3" rule is FDA-mandated and applies regardless of perceived bleeding risk or clinical frailty 1, 3
Renal Function Adjustments
CrCl >30 mL/min: Apply the standard "2-of-3" dosing algorithm above 2, 3
CrCl 15-29 mL/min: Automatically use 2.5 mg twice daily regardless of other criteria 2, 3
CrCl <15 mL/min or hemodialysis: FDA approves 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (only one criterion required in dialysis) 1, 3
Always calculate creatinine clearance using the Cockcroft-Gault equation, not eGFR, as this method was used in pivotal trials and FDA labeling 3, 2
Acute DVT/PE Treatment
- 10 mg orally twice daily for 7 days, then 5 mg orally twice daily for continued treatment 1, 4
- No dose adjustment for renal impairment, age, or weight during acute VTE treatment 1, 5
Reduction in Risk of Recurrent DVT/PE (Extended Prophylaxis)
- 2.5 mg orally twice daily after completing initial treatment course 1, 4
- This lower dose is used for long-term secondary prevention, not acute treatment 4
Postoperative VTE Prophylaxis (Hip or Knee Replacement)
- 2.5 mg orally twice daily starting 12-24 hours after surgery 1, 4
- Duration: 4
- Total hip replacement: 32-38 days
- Total knee replacement: 10-14 days
Critical Dosing Considerations
Common Prescribing Errors
- The most frequent error is inappropriate dose reduction based on a single criterion rather than requiring 2 of 3 criteria for atrial fibrillation 6, 3
- Studies show 9.4-40.4% of apixaban prescriptions involve underdosing, often driven by clinician concern about renal function or perceived bleeding risk when formal criteria are not met 3, 6
- Do not reduce the dose based on moderate CKD (CrCl 30-59 mL/min) alone unless the patient meets ≥2 dose-reduction criteria 3, 2
Pharmacokinetic Rationale
- Apixaban has only 27% renal clearance, making it the safest direct oral anticoagulant in renal impairment compared to dabigatran (≈80% renal) or rivaroxaban (≈66% renal) 7, 3
- This low renal dependence provides a wider safety margin as kidney function declines 3, 7
Drug Interactions Requiring Dose Adjustment
- Combined P-glycoprotein AND strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, itraconazole): Reduce from 5 mg to 2.5 mg twice daily 1, 2
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin): Avoid apixaban entirely as these markedly reduce drug levels 1, 3
Monitoring Requirements
- No routine INR monitoring is required 2, 3
- Reassess renal function at least annually, and every 3-6 months if CrCl <60 mL/min or evidence of declining function 2, 3
- Use the Cockcroft-Gault equation for all renal assessments, as eGFR and CrCl are not interchangeable and can lead to dosing errors 3, 2
Special Populations
Elderly Patients (≥80 Years)
- Age ≥80 years is one criterion only—requires a second criterion (weight ≤60 kg or serum creatinine ≥1.5 mg/dL) to justify dose reduction in atrial fibrillation 1, 3
- In dialysis patients, age ≥80 years alone is sufficient to reduce from 5 mg to 2.5 mg twice daily 3, 1
Low Body Weight (≤60 kg)
- Weight ≤60 kg is one criterion only—requires a second criterion to justify dose reduction in atrial fibrillation 1, 3
- In dialysis patients, weight ≤60 kg alone is sufficient to reduce from 5 mg to 2.5 mg twice daily 3, 1